Core Concepts
In this article you will be able to learn about the general viral life cycle and each of its steps, also about the viral lytic life cycle and the lysogenic cycle. After reading this article you will be able to understand how viruses enter cells and reproduce.
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Introduction to the Viral Life Cycle
For a virus to replicate and then proliferate, it first needs to enter a cell. There are 5 key steps during the viral life cycle, but depending on the type of virus, a different cycle will take place. These basic steps are attachment, penetration, gene replication and expression, assembly, and release.
Viruses
Viruses are infectious microorganisms that contain genetic material, such as RNA and DNA with a protein capsid. Due to their lack of capacity in reacting and act accordingly to their genetic material, viruses are not considered to be living organisms.
Viruses are most known for causing diseases and pandemics throughout human history, such as the Ebola outbreak in 2014 and the Coronavirus Pandemic in 2019. Still, these organisms have helped scientists to study and understand lots of cellular processes and protein synthesis.
5 Steps of the Viral Life Cycle
Attachment
For the virus to infect a host organism, the viral genome eventually has to transferred to the host cell cytoplasm. Then the viral life cycle starts when the virus recognizes and attaches to the cells’ receptors surface. This process involves two types of proteins:
- Attachment factors; recruit and holds viral particles and facilitating the interaction between entry receptors and viral particles.
- Viral receptors; promote the penetration of the virus into the cell. These receptors are specific for different viruses.
Viral receptors are very important to determine susceptibility to a virus and cell tropism. Host receptor factors can also determine cell tropism.
Penetration
The penetration process differs on enveloped or not viruses. Enveloped viruses can penetrate through direct fusion or receptor-mediated endocytosis, while non enveloped can only penetrate through receptor-mediated endocytosis.
- Direct fusion: In this mechanism two membranes fuse. The viral nucleocapsid is delivered to the cytoplasm, leaving the envelope on the plasma membrane. Retroviruses penetrate by this mechanism.
- Receptor-mediated endocytosis: By creating a coated pit on the plasma membrane, the virus particle-receptor complex initiates endocytosis, which results in the formation of endosomes. The virus particle is now located inside the endosome. The virus particle has to break the endosome to enter the cytoplasm. This process varies for enveloped or not viruses. For enveloped viruses acidic pH triggers a fusion between the endosomal membrane and viral envelope, causing the endosome to break. For nonenveloped viruses, capsid proteins induce endosome lysis.
Before entering to the gene replication and expression step, the virus needs to uncoat. The uncoating process exposes the viral genome to the cellular machinery for viral gene expression.
Gene Replication and Expression
Genome viral replication varies depending if the virus has RNA or DNA and if it has positive or negative nucleic acid polarity. Some viral genome even produces replicative proteins, such as the RNA-dependent RNA polymerase (RdRP) in SARS-CoV-2. Cell ribosomes can immediately translate viruses such as mRNA and +ssRNA. Other viruses like -ssRNA (negative nucleic acid single-stranded RNA) or dsRNA (double stranded RNA) need to carry their RdRP protein to undergo transcription.
Assembly
Capsid assembly and genome packaging are the two processes that occur during this stage. These two can occur simultaneously or sequentially, depending on the virus. A hole created in the procapsid structure is then used to package or insert the RNA genome. The viral capsid proteins then specifically detect a cis-acting element contained in the viral genome and package either RNA or DNA in response.
Release
The host cell releases the new viruses. Enveloped viruses bust off the cell by taking a portion of the host cell containing viral proteins. If not, the host cell lyses and releases the viral particles in their bare form.
The maturation of this new virus will occur extracellularly after the release. For rotaviruses and picornaviruses maturation is essential to acquire infectivity.
Viral Lytic Cycle
The difference between the lytic cycle and life cycle is basically that the viral lytic cycle involves the creation of more viruses on the inside of a host cell, which are eventually released from the cell, destroying it. On the other hand, during the life cycle the host cell releases the viruses and remains complete.
During the lytic cycle of virulent phages, bacteriophages take over the cell, reproduce and destroy it. Just as the general viral life cycle, this cycle consists of 5 key steps.
The first step of the infection is attachment. During this stage, the phage interacts with specific bacterial surface receptors. Most phages have a small host range and may only infect certain bacterial specie. The second step is the penetration. This process occurs by the contractions of a tail sheath, where the viral genome enters the cell wall and membrane. After this process the phage head and remaining parts linger outside the host.
The third step is biosynthesis of the new viral components. Bacterial chromosomes are degraded by viral-encoded endonucleases. The virus takes control of the cell and replicates, transcribes and translates all viral components to assemble a new virus. The fourth step is maturation. The bacterial wall is disrupted by proteins (holin or lysozyme) after new virions are formed. The final step is the release, where viruses are released in the lysis process. Progeny viruses are liberated to infect new cells.
Viral Lysogenic Cycle
A lysogen is when a bacteria has a prophage host, the prophage being when the phage’s genome has integrated into the cell. Finally, lysogeny is the process in which a bacterium is infected by a temperate phage.
In the lysogenic cycle, the phage genome enters by penetration and attachment. Different from the lytic cycle, the phage genome integrates into the chromosomes of the bacteria and becomes part of the host cell, not killing it. When the bacteria replicates its chromosomes it also replicates the phages genome, and when reproducing it passes the phages genome to its daughters. During the phage attachment, the bacteria may change its phenotype because phages can add extra genes. This process is a lysogenic conversion/phage conversion. While the lysogeny process is still going, the prophage will continue at the chromosome of the bacteria until the induction process. The induction process will result in the removal of the viral genome of the host chromosomes. Finally, the tempered phage can proceed to a lytic cycle or undergo lysogeny in some new cells.
We can see the process summarized in the following image:
- Phage infects the cell.
- Phages DNA incorporates the host DNA
- The Prophage genome passes to daughter cells throughout cell replication.
- Cell enters the lytic cycle and the chromosome is now prophage DNA free.
- Phages replicate and their proteins are synthesized.
- The protein and phages are assembled and they release.
Retroviruses
A retrovirus is a ribonucleic acid (RNA) virus that possesses an enzyme on its capsid, called reverse transcriptase, that converts the genetic material into deoxyribonucleic acid (DNA) when it enters a living organism cell. This +ssRNA (single-stranded RNA)viruses have a different life cycle than the general virus.
The reverse transcriptase synthesizes a complementary DNA, called ssDNA, using the +ssRNA as a genome mold. The ssDNA is made into dsDNA. Then the genetic material integrates permanently into the host cell’s chromosomes, now calling it provirus or proviral DNA. The virus now is a permanent host in the cell, generating a chronic infection.
